Molecular dynamics and mechanics calculations on a DNA duplex with A(+)-C, G-T and T-C mispairs

Despite major advances in characterizing purine(R)-purine(R), purine(R)-pyrimidine(Y) and pyrimidine(Y)-pyrimidine(Y) mismatches in DNA, there have not been any structural studies on a synthetic DNA duplex containing several different mispairs. Here, using NMR restrained molecular mechanics and dynamics simulations we have structurally characterized a 12 nucleotide long antiparallel DNA duplex with three different mispairs, namely A+-C, G-T and T-C. Our results show that the overall conformation of the antiparallel DNA duplex is B-DNA-like with slight structural distortions at or near the mispairs' sites. All these mispairs are properly stacked with their flanking base pairs. Each mispair is stabilized by two hydrogen bonds and the decreasing order of the hydrogen-bonding interactions is G-T>T-C>A+-C. G-T mispair has smaller configurational space while the structure is slightly bent at A+-C mispair's site. Overall, this study is the first ever structural characterization of a DNA duplex with three different mismatched base pairs and throws light upon the local conformations of the three mispairs present in the DNA duplex.